In part 3 of this Frontline Forum series, Brent Moody, MD; Sarah Arron, MD, PhD; Justine Cohen, DO; Emily Ruiz, MD, MPH; and Todd Schlesinger, MD, discuss non-surgical treatment options for the management of BCC, dose adjustments for systemic treatments, combining hedgehog pathway inhibitors with immunotherapy, and more.
Ruiz noted that the type of skin cancer is the major factor in her decision to pursue nonsurgical treatment, and she has found that Mohs surgery is usually the easiest treatment for patients with BCC. However, the multidisciplinary team, the patient, and the patient’s family should all be involved in the decision-making process. Ruiz shared that when her institution implemented a multidisciplinary tumor board in 2020, it appeared to improve the patient experience and outcomes as well as the quality of care provided by the multidisciplinary team members.
“Thinking about the options up front in advance of attempting a surgery has helped us better define where is that the best option and where should we be doing something else,” she said. “The patient recognizes in advance that it may not be as successful. It reaffirms what you’re doing, and it reaffirms to the patient that this is the best approach.”
Moody added that being part of a multidisciplinary team and participating in tumor board discussions has made him a better dermatologist and Mohs surgeon because it has improved his understanding of situations in which nonsurgical cancer treatments are appropriate. He encourages other dermatologists to hold regular meetings (virtual if necessary) with the team members to discuss cases.
Considerations for Selection of Systemic Therapy
Arron noted that a hedgehog pathway inhibitor (eg, vismodegib or sonidegib) is typically considered the first-line option for systemic treatment of BCC (unless it is inappropriate or intolerable for the patient). However, she said there is significant leeway for considering the immunotherapy drug cemiplimab, an intravenously administered PD-1 inhibitor approved for treatment of patients with locally advanced or metastatic BCC who previously received (or are ineligible for) a hedgehog pathway inhibitor, because it is often more tolerable.4 Although the potential adverse events (AEs) associated with immunotherapy (eg, thyroiditis or pneumonitis) tend to be more severe than the AEs linked to hedgehog pathway inhibitors (eg, change in taste or hair loss), Arron noted that the latter drugs’ AEs more severely impact quality of life, which may negatively impact adherence. Therefore, she sets aside ample time with patients to discuss the benefits and drawbacks of both systemic options. Additionally, she refers patients to an oncologist for a more detailed discussion.
Ruiz said that, if given a choice, she would prefer to first give immunotherapy over a hedgehog pathway inhibitor because the response, if it occurs, is often more durable. Moreover, long-term use of hedgehog pathway inhibitors can lead to development of resistance against all members of this class of drug. However, hedgehog pathway inhibitors may be advantageous in scenarios where a quick response is needed, such as a tumor that is encroaching on the spinal cord or an eye.
Patient factors should also influence systemic therapy decisions, said Zeitouni. For example, a hedgehog pathway inhibitor may be preferable for a patient who has difficulty attending regular doctors’ appointments for infusions and blood work, whereas immunotherapy may be better for a patient who has difficulty taking oral medication regularly at home. Medical oncologists may also prefer hedgehog pathway inhibitors to treat younger patients to avoid the possibility of lifelong immune-related AEs, such as hypothyroidism or adrenal deficiency.For patients who decide to start immunotherapy for BCC, Zeitouni typically stays in contact with the medical oncologist overseeing the treatment to check on the patient’s response and schedules a follow-up visit to assess whether the target outcome was achieved.
The optimal duration of immunotherapy is still unclear, although most of the panelists said they typically continue treatment for 1 year if the patient has a complete or partial response and is tolerating it well. According to Moody, clinical follow-ups are adequate to monitor patients with clinically accessible tumors, whereas radiographic assessment may be indicated for patients with radiographic extension or medial tumors.
Future Directionsin BCC Treatment
“Advanced BCC cases are complex and unique because of differences in tumor-, location-, and psychosocial-related characteristics; therefore, identification of biomarkers that predict response to therapy could help identify optimal treatment sequences and improve standardization of therapy for patients with given characteristics,” said Arron. Ruiz noted that additional systemic treatment options for BCC are also needed when currently available ones fail to yield a response. Studies investigating therapeutic combinations that increase the immunogenicity of the tumor may also improve responses seen with cemiplimab.
There are several factors needed to maximize the multidisciplinary BCC care team’s success, according to Schlesinger. He concluded that identifying dermatologists in the community who are comfortable with managing advanced BCC, including a medical oncologist as a joint partner for treatment regimens involving infusions, and improving text-based communication among members of the multidisciplinary team through Health Insurance Portability and Accountability Act–compliant platform are critical for best patient outcomes.
4. Libtayo. Prescribing information. Regeneron Pharmaceuticals Inc; 2021. Accessed July 21, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf.